A B-D-Glucan Driven Antifungal Stewardship Approach for Invasive Candidiasis

August 26, 2024 updated by: Maddalena Giannella, University of Bologna

A B-D-Glucan Driven Antifungal Stewardship Approach to Manage Empirical Therapy in Patients at Very High Risk for Invasive Candidiasis: a Randomized Controlled Trial

This is a multicenter, prospective, open-label, randomized trial. Patients with severe abdominal condition developing severe sepsis or septic shock and receiving broad spectrum antibiotic and antifungal treatment will be randomized (1:1) to:

  1. discontinue antifungal treatment based on negative (<80 pg/ml) result of 1,3 beta-d-glucan performed on day 0,3,6 and 10
  2. continue antifungal treatment according with attending physician's decision.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Primary objective:

Our objective is to establish whether a strategy based on beta-d-glucan (BG) assessment could achieve reduced antifungal consumption in patients with severe abdominal condition developing severe sepsis and septic shock without any impact on the outcome Secondary objectives i) Assess the accuracy of BG in the diagnosis of invasive candidiasis (IC) in in critically ill patients with a severe abdominal condition who develop severe sepsis or septic shock.

ii) Describe the changes over the time of BG value according with colonization status, infection or none the aforementioned events.

Material and Methods Study design: a multicenter, open label, randomized trial Population: all the patients with a severe abdominal condition who develop a severe sepsis or septic shock.

  1. Inclusion Criteria:

    1. adult (≥ 18 year) patients;
    2. signed informed consent before surgical procedure;
    3. severe sepsis or septic shock;
    4. at least one of the following conditions: i) post-operative peritonitis, ii) recurrent gastrointestinal perforation, iii) post-operative hepatobiliary and/or pancreatic disorders including necrotizing pancreatitis, iv) post-operative intra-abdominal abscess, and v) anastomotic leak.
  2. Exclusion criteria a. diagnosis of candidiasis before the enrollment b. exposure in the past 30 days to any antifungal treatment or diagnosis of invasive fungal infection; c. pregnancy or lactation; d. history of allergy to any of the antifungal drugs; e. major immunosuppression conditions including: i. neutropenia (<0.5 × 109 neutrophils/L [<500 neutrophils/mm3] for >10 days), ii. receipt of an allogeneic stem cell transplant or solid organ transplantation, iii. inherited severe immunodeficiency (such as chronic granulomatous disease or severe combined immunodeficiency), iv. HIV infection with lymphocyte T CD4+ cell count < 200/mmc. f. patients with poor prognosis or unable to sign informed consent.

Procedures Pre-randomization procedures

At the time of patient enrollment (within 24 h from onset of severe sepsis/septic shock), a standardized diagnostic work-up must be performed including at least:

i) two sets of blood cultures; ii) 5 surveillance cultures (rectal swab, urine culture, pharyngeal swab, axillary swab, groin swab).

iii) in case of re-intervention or percutaneous drainage: Gram stain and culture of intra-abdominal samples; iv) serum BG determination. Antibiotic and antifungal empirical therapy should be started immediately after collection of microbiological samples according with a predefined standard of care (see appendix 1). Once completed this procedures patients will proceed to randomization.

Randomization Patient eligible for the study after the beginning of antifungal therapy will be randomized 1:1 to receive (Group A) a BG driven de-escalation strategy or (Group B) a course of antifungal treatment based on the care provider's decision.

In both groups, if cultures yield invasive candidiasis (see below) the patient will be managed in according with guidelines and excluded from the per-protocol analysis.

In both groups, BG determination will be repeated at day +3, +6 and +10 after starting antifungal therapy.

Randomization will be carried out providing closed envelopes to the participating centers immediately before the study onset.

Study Type

Interventional

Enrollment (Actual)

34

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Bologna, Italy, 40138
        • Azienda Ospealiero Universitaria di Bologna Policlinico S.Orsola-Malpighi

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • a. adult (≥ 18 year) patients; b. signed informed consent before surgical procedure; c. severe sepsis or septic shock; d. at least one of the following conditions: i) post-operative peritonitis, ii) recurrent gastrointestinal perforation, iii) post-operative hepatobiliary and/or pancreatic disorders including necrotizing pancreatitis, iv) post-operative intra-abdominal abscess, and v) anastomotic leak.

Exclusion Criteria:

  • a. diagnosis of candidiasis before the enrollment b. exposure in the past 30 days to any antifungal treatment or diagnosis of invasive fungal infection; c. pregnancy or lactation; d. history of allergy to any of the antifungal drugs; e. major immunosuppression conditions including: i. neutropenia (<0.5 × 109 neutrophils/L [<500 neutrophils/mm3] for >10 days), ii. receipt of an allogeneic stem cell transplant or solid organ transplantation, iii. inherited severe immunodeficiency (such as chronic granulomatous disease or severe combined immunodeficiency), iv. HIV infection with lymphocyte T CD4+ cell count < 200/mmc. f. patients with poor prognosis or unable to sign informed consent.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: De-escalation

In this group, investigators will manage the antifungal therapy according to the BG levels as follows:

  1. antifungal therapy will be stopped immediately after the BG response in case of serum BG <80 pg/ml in presence of clinical stability (CS);
  2. antifungal therapy will be continued until further BG determination, both for BG levels between 80-200 pg/ml and for BG <80 pg/ml in patients without CS. In these cases, if the following BG value is <80 pg/ml antifungal therapy will be stopped independently from the CS achievement.
  3. antifungal therapy will be continued until day 10 for BG levels >200 pg/ml
Diagnostic test: De-escalation
Antifungal therapy will be stopped according with BG results
No Intervention: Standard of care

In this group antifungal treatment will be continued until clinician's decision.

Investigators will be blinded to the BG levels of patients enrolled in this arm, The BG results will be faxed directly to the coordinating center.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Antifungal consumption
Time Frame: 28 days
Days of antifungal consumption will be compared between the two groups
28 days
Mortality
Time Frame: 28 days
28-day mortality will be compared between the two groups
28 days
Length of stay
Time Frame: 28 days
Length of stay in ICU will be compared between the two groups
28 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Accuracy of BG
Time Frame: 28 days
sensitivity, specificity, positive predictive value, negative predictive value of BG in the diagnosis of invasive candidiasis
28 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Bologna

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2017

Primary Completion (Actual)

June 10, 2019

Study Completion (Actual)

June 10, 2019

Study Registration Dates

First Submitted

March 18, 2017

First Submitted That Met QC Criteria

March 18, 2017

First Posted (Actual)

March 24, 2017

Study Record Updates

Last Update Posted (Actual)

August 28, 2024

Last Update Submitted That Met QC Criteria

August 26, 2024

Last Verified

August 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BDG-ETHIC

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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